The conformations, microdynamic behavior, and interactions with biologically important receptors (acceptors) of peptide hormones, analogues, and derivatives will be examined using a combination of biophysical techniques, synthetic organic chemistry, and biological assay methods. The relationships between biological activity and the conformational and microdynamic properties of the peptides will be sought, and the results will be used as a basis for preparing better hormone antagonists and more specific agonists, and for examining the physical-chemical basis for hormone action. Specifically labeled (2H, 13C, 14C, 15N, 19F, etc.) amino acids and amino acid derivatives will be prepared and incorporated into the neurohypophyseal hormones, related analogues, and other peptide hormones. These compounds will be used in studies of their conformational and microdynamic behavior, and of their interactions with biologically significant macromolecules such as the neurophysin proteins found in neurosecretory granules. Nuclear magnetic resonance spectroscopy, circular dichroism and laser Raman spectroscopies, membrane receptor binding, affinity labeling methods, and other biochemical and biophysical methods will be used to develop an understanding of peptide hormone action at the molecular level. A variety of biological assays such as milk ejecting, uterine contracting, frog skin darkening, and melanoma adenylate cyclase will be used to assess biological effects. The design and synthesis of hormone with analogues with properties useful for medical & other applications will be sought with special emphasis on melanophore stimulating hormone analogues suitable for melanoma localization studies and oxytocin analogues which will be potent antagonists of oxytocin at uterine and mammary tissue.